Project highlights: a first-in-class inhibitor series exemplified by probe ML216 has been developed. Inhibitors induce SCEs and show anti-proliferative activity in cells containing BLM but not in otherwise isogenic BLM-deficient cells. Combination studies with BLM-targeting compounds for anticancer therapy are being explored. During this period, the NCGC has fostered and maintained over 180 active collaborations with both NIH and extramural investigators, facilitating drug discovery efforts across the entire spectrum of human disease. These efforts have led to over 100 high-throughput screens and nearly 60 medicinal chemistry campaigns, providing our collaborators and the general research community a wealth of publications and promising small molecule leads. In addition, the NCGC has undertaken a number of informatic challenges to make better use of existing drug and disease target information and provide the general public with easily accessible resources, further catalyzing the development of new therapies for human disease.